Polynucleotide arrays (such as DNA or RNA arrays) and peptide array, are known and may be used, for example, as diagnostic or screening tools. Such arrays include regions (sometimes referenced as spots or features) of usually different sequence polynucleotides or peptides arranged in a predetermined configuration on a substrate. The array is “addressable” in that different features have different predetermined locations (“addresses”) on a substrate carrying the array.
Biopolymer arrays can be fabricated using in situ synthesis methods or deposition of the previously obtained biopolymers. The in situ fabrication methods include those described in U.S. Pat. No. 5,449,754 for synthesizing peptide arrays, and in U.S. Pat. No. 6,180,351 and WO 98/41531 and the references cited therein for polynucleotides. In situ methods also include photolithographic techniques such as described, for example, in WO 91/07087, WO 92/10587, WO 92/10588, and U.S. Pat. No. 5,143,854. The deposition methods basically involve depositing biopolymers at predetermined locations on a substrate which are suitably activated such that the biopolymers can link thereto. Biopolymers of different sequence may be deposited at different feature locations on the substrate to yield the completed array. Procedures known in the art for deposition of biopolymers, particularly DNA such as whole oligomers or cDNA, are described, for example, in U.S. Pat. No. 5,807,522 (touching drop dispensers to a substrate), and in PCT publications WO 95/25116 and WO 98/41531, and elsewhere (use of a pulse jet in the form of a piezoelectric inkjet head).
Further details of large scale fabrication of biopolymer arrays by depositing either previously obtained biopolymers or by the in situ method, are disclosed in U.S. Pat. Nos. 6,242,266, 6,232,072, 6,180,351, and 6,171,797.
In array fabrication, the quantities of DNA available for the array are usually very small and expensive. Sample quantities available for testing are usually also very small and it is therefore desirable to simultaneously test the same sample against a large number of different probes on an array. These conditions require the manufacture and use of arrays with large numbers of very small, closely spaced features.
The arrays, when exposed to a sample, will exhibit a binding pattern. The array can be read by observing this binding pattern by, for example, labeling all targets such as polynucleotide targets (for example, DNA), in the sample with a suitable label (such as a fluorescent compound), scanning an illuminating beam across the array and accurately detecting the fluorescent signal from the different features of the array. Assuming that the different sequence polynucleotides were correctly deposited in accordance with the predetermined configuration, then the observed binding pattern will be indicative of the presence and/or concentration of one or more polynucleotide components in the sample. Peptide or arrays of other chemical moieties can be used in a similar manner. Techniques and apparatus for scanning chemical arrays have been described, for example, in U.S. Pat. Nos. 5,763,870 and 5,945,679. Apparatus which reads an array by scanning an illuminating beam by the foregoing technique are often referred to as scanners and the technique itself often referred to as scanning. Conventionally, such scanning has been done by illuminating array features on a front surface of the substrate one pixel at a time. Array scanners typically use a laser beam as a light source, which is scanned over pixels covering the array features. A detector (typically a fluorescence detector) with a very high light sensitivity is normally desirable to achieve maximum signal-to-noise in detecting hybridized molecules, particularly in array scanners used for DNA sequencing or gene expression studies. At present, photomultiplier tubes (“PMTs”) are still the detector of choice although charge coupled devices (“CCDs”) and avalanche photodiodes (“APDs”) can also be used. PMTs and APDs are typically used for temporally sequential scanning of array features, while CCDs permit scanning many features in parallel (for example, one line of features simultaneously, in which case an illuminating line may be used).
Polynucleotide arrays have previously been provided in two formats (sometimes referenced as “array units”). In one format, the array is provided as part of a package in which the array itself is disposed on a first side of a glass or other transparent substrate. This substrate is fixed (such as by adhesive) to a housing with the array facing the interior of a chamber formed between the substrate and housing. An inlet and outlet may be provided to introduce and remove sample and wash liquids to and from the chamber during use of the array. The entire package may then be inserted into a laser scanner, and the sample exposed array may be read through a second side of the substrate.
In another format, the array is present on an unmounted glass or other transparent slide substrate. This array is then exposed to a sample optionally using a temporary housing to form a chamber with the array substrate. The slide may then be placed in a laser scanner to read the exposed array. Most slide scanners require that the user manually insert the slide into a holder within the scanner. Some scanners allow the slide to rest on a surface while others clamp it to a known location using various types of guides. However, this exposes the fragile slide to the risk of chipping or breaking with consequent loss of what may be a very expensive array which itself may carry the results of an expensive and difficult to reproduce experiment. Perhaps even worse, minor damage such as smudges or scratches may go unnoticed to a user but can cause highly erroneous results to be read from the very small features of the array.
One of the problems recognized by the present invention, of using array holders, is as follows. First, different manufacturers may wish to construct array holders of different configurations (for example, to include a hybridization chamber). This can lead to a problem in that different array holders may position the array substrate, and hence the array, at different spatial locations within the scanner depending on the particular dimensions of the array holder. To avoid wasted time and misleading data, the scanner is set to scan only the area of the array on the slide. To do this the scanner needs to know where the array is physically located inside the scanner. Knowing where the array is located inside the scanner also avoids misinterpretation of read data as a result of incorrectly assuming that a location in a scanned image (for example, a corner feature) is the actual location on the array (for example, the corner). While this may not be a problem if all users were to use a standard size slide for all arrays (such as the well accepted 1″×3′ microscope slide), the introduction of various non-standardized holders causes the array location within the scanner to vary. Another problem recognized by the present invention is that some scanners may not actually be able to physically accommodate some holders and could be damaged by their attempted loading into the scanner. Further, to keep array manufacturing costs low, it may be desirable to use non-standard substrate sizes in which case it becomes useful for the scanner to know in advance both the location and the size of the substrate containing the array. This can be particularly important where it is possible to damage the reader or holder should reader attempt to read an area (such as by laser illumination of it) where no substrate is present.
The present invention recognizes that it would be desirable then to have some means for an array reader to obtain information on one or more characteristics of an array holder or an array unit.